Structure and functions of the molecules which are recognized by the anti-neural antibodies in paraneoplastic neurological syndrome

副肿瘤性神经系统综合征是癌症对神经系统的远程影响，是癌症非转移性并发症中最不常见的。目前的证据表明，一些副肿瘤综合征患者的血清和脑脊液中存在与神经元和肿瘤反应的自身抗体。我们用患者血清进行免疫筛选，从人脑文库中分离出一个cdna克隆“CZF”和“huv”并对其进行了鉴定。我们发现与副肿瘤性小脑变性(PCD)相关的克隆“CZF”具有锌指动机，与副肿瘤性感觉神经病相关的克隆“huv”具有DNA结合位点和CAG三重重复。这些克隆可能会影响转录，而转录对维持神经细胞很重要。我们制备了每个重组部分蛋白，与WECH患者血清反应，并产生抗体。“CZF”和“huv”的全长cDNA克隆仍在进行中。我们检测了这些患者和抗Hu抗体患者的免疫球蛋白对培养的神经母细胞瘤细胞株的影响，发现在正常条件下几乎没有作用。我们制备了重组的部分HUD蛋白，并建立了检测患者血清和脑脊液中抗Hu抗体的免疫印迹和ELISA体系。这些系统有助于癌症筛查，特别是小细胞肺癌的筛查，以及监测化疗或癌症复发的效果。

Paraneoplasitic neurological syndrome is the remote effects of cancer on the nervous system which is the least common of the nonmetastatic complication of cancer. Present evidence suggests that some patients with paraneoplastic syndromes harbor autoantibodies in the serum and CSF that react with neuronal elements as well as with tumors.We isolated a cDNA clones "CZF" and "HuV" from a human brain library by immunoscreening using patients' sera and characterized them. We found that the clone "CZF" associated with paraneoplastic cerebellar degeneration (PCD) had zinc finger motives and the clone "HuV" associated with paraneoplastic sensory neuropathy had DNA binding sites and CAG triple repeats. These clones may affect transcription which is important to maintain neuronal cells. We made each recombinant partial protein, which was reacted by wech patient's serum, and produced antibody against each. Whole length cDNA cloning of "CZF" and "HuV" is still underway. We examined the effects of IgG from these and patient with anti-Hu antibody on cultured neuroblastoma cell line and found little effects in normal condition.We produced recombinant partial HuD protein, and established immunoblot and ELISA systems for detection of anti-Hu antibody in the serum and CSF of patients. These systems were useful for screening of cancer, especially of small cell lung cancer, and monitoring the effects of chemotherapy or recurrence of cancer.